Jiangsu Simcere Pharmaceutical R and D Co.

Nanjing, China

Jiangsu Simcere Pharmaceutical R and D Co.

Nanjing, China
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Fu Z.,Macau University of Science and Technology | Fu Z.,Jiangsu Simcere Pharmaceutical R and D Co. | Chen X.,Nanjing University | Guan S.,Nanjing University | And 5 more authors.
Oncotarget | Year: 2015

Curcumin, a natural polyphenol compound from the perennial herb Curcuma longa, has been proved to be beneficial for tumor-bearing animals through inhibiting tumor neovasculature formation, but the underlying mechanisms are unclear. Here, we aim to test whether curcumin affects VEGF-VEGFR2 signaling pathway and attenuates defective hematopoiesis induced by VEGF in tumor model. We demonstrated that curcumin inhibited proliferation, migration of HUVEC under VEGF stimulation and caused HUVEC apoptosis, and blocked VEGFR2 activation and its downstream signaling pathways in vitro. Furthermore, in VEGF over-expressing tumor model, curcumin significantly inhibited the tumor growth accelerated by VEGF in a dose-dependent manner and improved anemia and extramedullary hematopoiesis in livers and spleens of tumor-bearing mice induced by tumor-derived VEGF. Immunohistochemical analysis showed that curcumin normalized vasculature structures of livers and reduced tumor microvessel density. ELISA revealed that curcumin suppressed VEGF secretion from tumor cells both in vitro and in vivo. Survival analysis showed that curcumin significantly improved survival ability of VEGF tumor-bearing mice. Taken together, these findings establish curcumin as a modulator of VEGF and VEGF-VEGFR2 signaling pathway, with potential implication for improving the quality of life of cancer patients.

Huang W.,Jiangsu Simcere Pharmaceutical RandD Co. | Huang W.,Nanjing University | Tan A.,Jiangsu Simcere Pharmaceutical RandD Co.
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

In the title compound, C15H12FN3O 3·CH3OH, the dihedral angle between the quinazoline ring system and the benzene ring is 81.18 (9)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯N hydrogen bonds, generating [10-1] chains of alternating main mol-ecules and solvent mol-ecules. Weak C-H⋯O inter-actions are also observed.

Yang H.,Nanjing University | Zhang H.,Nanjing University | Zhu L.,Jiangsu Simcere Pharmaceutical R and D Co. | Wang J.,Nanjing University | And 2 more authors.
International Journal of Oncology | Year: 2012

Carcinogenesis is a multi-step process, which includes oncogene activation, mutation silencing of tumor suppressor genes, impairment of chromosomes or epigenetic changes such as CpG island methylation through various cellular pathways, involving a series of somatic genetic alterations. Furthermore, miRNAs present a mechanism by which genes with diverse functions on multiple pathways can be simultaneously regulated at the post-transcriptional level. However, little is known about the cancer-related pathways through which cancer-associated miRNAs (CA-miRNAs) regulate these processes representing either positive or negative functions in carcinogenesis. This study investigated eleven miRNAs previously identified cancer-related regulators. Using function and pathway analysis of their targeted genes, the relevance of miRNA regulation the induction of cancer can be observed. The results showed that CA-miRNAs may function in the post-transcriptional level mainly through manipulating the expression of transcription factors and protein kinases, and target genes for the CA-miRNAs were most prominently predicted to function the regulation of transcription. Our analysis also highlighted the potential of these CA-miRNAs to regulate the cell differentiation, proliferation, endocytosis and migration signaling logically required to cause a cancer cell mainly through five canonical pathways. Combined with previous cancer studies, the analysis of the relevance between functions of CA-miRNAs and cancer-related pathways exploring different internal carcinogenesis stimuli also revealed the potential of the top five pathways to regulate core carcinogenesis processes. These findings should form a useful knowledge base for potential future development of novel therapeutic treatments.

Liu J.,Jiangsu Simcere Pharmaceutical RandD Co. | Liu J.,China Pharmaceutical University | Feng L.,Jiangsu Simcere Pharmaceutical RandD Co. | Li H.-D.,Jiangsu Simcere Pharmaceutical RandD Co. | And 2 more authors.
Helvetica Chimica Acta | Year: 2012

Three new ent-kaurane glucopyranosides, 2-O-[β-D-apiofuranosyl- (1→3)-2-O-isovaleryl-β-D-glucopyranosyl]-4-epi-atractyligenin (1), 2-O-[β-D-apiofuranosyl-(1→3)-2-O-isovaleryl-β-D-glucopyranosyl] atractyligenin (2), and 2-O-[β-D-apiofuranosyl-(1→3)-2-O-(3- methylpentanoyl)-β-D-glucopyranosyl]-4-epi-atractyligenin (3), along with 2-O-(2-O-isovaleryl-β-D-glucopyranosyl)-4-epi-atractyligenin (4), were isolated for the first time from the aerial parts of Siegesbeckia pubescens. The structures were established by extensive spectroscopic analyses including 1D- and 2D-NMR (HSQC, HMBC, and ROESY), and HR-ESI-MS, and by comparison with published data. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich, Switzerland.

Zhang H.,Jiangsu Simcere Pharmaceutical R and D Co. | Tan A.-M.,Jiangsu Simcere Pharmaceutical R and D Co. | Zhang A.-Y.,Jiangsu Simcere Pharmaceutical R and D Co. | Chen R.,Jiangsu Simcere Pharmaceutical R and D Co. | And 2 more authors.
Steroids | Year: 2010

Five new C21 steroidal glycosides (1-5) were isolated from the stems of Marsdenia tenacissima. The chemical structures and relative configurations of the new compounds were elucidated by mass spectrometry and NMR spectroscopy. Cellular assay of these compounds showed that they are weak cytotoxic to various cell lines. © 2009 Elsevier Inc. All rights reserved.

Wang R.,Jiangsu Simcere Pharmaceutical R and D Co. | Wang G.-J.,China Pharmaceutical University | Wu X.-L.,China Pharmaceutical University | Zhou F.,China Pharmaceutical University | Li Y.-N.,China Pharmaceutical University
Chinese Journal of Natural Medicines | Year: 2013

Aim: Although ginsenoside Rg1 possesses potent neuroprotective effects, it cannot easily be transported to brain parenchyma because of the blood-brain barrier (BBB). This study was aimed to verify the hypothesis that the ginsenoside Rg1 neuroprotective effect might be mainly derived from its direct protective effects on BBB. Methods: Male Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) by using the suture insertion method followed by 22 h of reperfusion. In the Rg1-treated group, Rg1 (45 mg·kg-1) was administrated via tail venous (i.v.) 1 h before focal ischemia and 3 h after reperfusion. The integrity of the BBB was measured in vivo, MDA and SOD were estimated in vitro. The expression and activity of matrix metalloproteinases (MMPs), and the expression of tissue inhibitor of matrix metalloproteinases (TIMPs) mRNA, were determined to evaluate the protective effect of Rg1 on BBB structure both in vivo and in vitro. Results: In ischemia/reperfusion rats, using the EB dye extravasation, the expression and activity of MMPs were increased as compared to sham rats, while in Rg1-treated rats, these increases were inhibited. The expression of TIMP-2 mRNA in the ischemia/reperfusion rats was decreased as compared to sham rats, while in Rg1-treated rats, these decreases were ameliorated. The results of in vitro models were consistent with those of in vivo models. Conclusion: Ginsenoside Rg1 may exert its protective effect of CNS indirectly by protecting the structure of the BBB, through protecting BMECs and reducing the expression and activity of MMPs in pathological conditions. © 2013 China Pharmaceutical University.

Guo W.,Jiangsu Simcere Pharmaceutical R and D Co. | Li J.-H.,Jiangsu Simcere Pharmaceutical R and D Co. | Wang F.,Jiangsu Simcere Pharmaceutical R and D Co.
Chinese Journal of Evidence-Based Medicine | Year: 2013

Objective To evaluate the effectiveness and safety of nedaplatin combined with chemotherapy versus cisplatin combined with chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods The randomized controlled trials (RCTs) on nedaplatin combined with chemotherapy versus cisplatin combined with chemotherapy for advanced NSCLC were searched in The Cochrane Library, PubMed, EMbase, CBM, VIP and WanFang Data from the date of their establishment to January 2012. According to the inclusion and exclusion criteria, two reviewers independently screened the studies, extracted the data and assessed the quality. Then RevMan 5.0 software was used for meta-analysis. Results A total of 15 RCTs involving 1 076 patients were included. The results of meta-analysis showed that, compared with the cisplatin combined with chemotherapy, nedaplatin combined with chemotherapy could reduce the risks of nausea and vomiting (RR=0.56, 95%CI 0.48 to 0.65, P<0.000 01), decrease the risk of renal function impairment (RR=0.47, 95%CI 0.30 to 0.74, P=0.001), but increase the risk of thrombocytopenia (RR=1.59, 95%CI 1.20 to 2.11, P=0.001). There were no significant differences between the two groups in objective response rate (ORR) (RR=1.09, 95%CI 0.92 to 1.29, P=0.03), leukopenia (RR=1.05, 95%CI 0.92 to 1.19, P=0.50), and hemoglobin reduction (RR=0.92, 95%CI 0.80 to 1.07, P=0.30). Conclusion Compared with cisplatin combined with chemotherapy for advanced NSCLC patients, nedaplatin in combination with chemotherapy can significantly reduce the risks of nausea, vomiting and renal function impairment. Although the ORRs are similar in the two groups, nedaplatin combined with chemotherapy can cause a higher risk of thrombocytopenia. For the quality restriction and possible publication bias of the included studies, more high quality RCTs are required to further verify this conclusion. © 2013.

Wang S.,China Pharmaceutical University | Wang S.,Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research | Lv J.,China Pharmaceutical University | Lv J.,Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research | And 7 more authors.
Cancer Immunology, Immunotherapy | Year: 2012

Co-stimulatory molecules can be efficiently produced as a recombinant protein in E. coli with a large range of applications in the fields of immunotherapy. However, whether, different fusions that would affect their functions have rarely been analyzed. To explore the effects of different fusions and linkers on the molecular conformation and activity of CD137 ligand (CD137L), a recombinant human CD137L protein (rhCD137L) library, which consists of the entire extracellular domain of human CD137L fused to N- or C-terminal His-tag through different linkers, was constructed and all rhCD137Ls were, respectively, expressed in E. coli BL21 (DE3) strain carrying a chaperone plasmid pG-Tf2. After purification of the soluble rhCD137Ls, the recombinant fusion proteins could markedly promote the growth of activated T cells, but their effects on cytokine productions were different from each other. The present work indicated that, although all rhCD137Ls have desired biological activity, different fusions and linkers did affect their structures and functions. Consequently, rational design of a library is a necessary and feasible approach for fusion proteins in order to obtain a satisfactory drug candidate for further development. © Springer-Verlag 2011.

Yu S.,Jiangsu Simcere Pharmaceutical R and D Co. | Yu Y.,China Pharmaceutical University | Liu L.,China Pharmaceutical University | Wang X.,China Pharmaceutical University | And 5 more authors.
Planta Medica | Year: 2010

Our previous study showed a higher exposure of berberine, palmatine, coptisine, epiberberine and jatrorrhizine in 6-week streptozotocin (STZ)-induced diabetic rats, after oral administration of Coptidis Rhizoma extract. The aim of the present study was to investigate whether the function and expression of intestinal P-glycoprotein (PGP) was downregulated in STZ-induced diabetic rats and if the impairment of PGP function and expression contributed to the exposure increase of the five protoberberine alkaloids. Plasma concentration-time profiles of the drugs in the portal vein were obtained after oral administration of Coptidis Rhizoma extract. The effective permeability of the drug across duodenum and ileum were measured using in situ single-pass intestine perfusion. PGP function in the rat intestine was assessed by measuring the absorption of rhodamine 123 (Rho123). PGP levels were evaluated using Western blots. It was found that the Cmax and AUC0-8 values of five alkaloids in the portal vein of diabetic rats were significantly higher than those in the control rats. Diabetic rats also exhibitd a higher level of Rho123 in the portal vein, which showed impairment of PGP function. A higher effective permeability of the tested drug was found in the duodenum of diabetic rats using in situ single-pass intestine perfusion, indicating that berberine and Rho123 transported more easily across the intestinal barrier of diabetic rats. A lower level of PGP protein was found in the duodenum, jejunum and ileum of the diabetic rats as compared with age-matched control rats. All these results suggested that the function and expression of PGP were impaired in the intestine of STZ-induced diabetic rats which, at least partly, contributed to the exposure increase of the five protoberberine alkaloids. © Georg Thieme Verlag KG Stuttgart New York•.

Tong Y.,China Pharmaceutical University | Zhong K.,China Pharmaceutical University | Tian H.,China Pharmaceutical University | Gao X.,China Pharmaceutical University | And 3 more authors.
International Journal of Biological Macromolecules | Year: 2010

In this study, we investigated the PEG attachment site of mono-PEGylated Endostar, a modified recombinant human endostatin approved in China for lung cancer. N-terminal site-directed mono-PEGylation of Endostar was accomplished using mPEG-propionaldehyde derivatives (Mw = 20 kDa) under slightly acidic pH conditions (pH 5.5). One-step cation exchange chromatography was used to purify the mono-PEGylated Endostar. Following tryptic digestion, the peptide fragment containing PEG was separated by SDS-PAGE. Barium iodide staining and Western blotting were used to detect the PEG moiety and the N-terminus of Endostar, respectively. The peptide fragment stained by barium iodide showed a positive response to anti-(His) 6 mAb, demonstrating that PEG was located at the N-terminus of Endostar. LC/MS was applied to verify the occurrence of mono-PEGylation at the N-terminus of Endostar. © 2010 Elsevier B.V. All rights reserved.

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